Depression and Stroke Disease

Both psychosocial and physical factors appear to be of importance in the development of post-stroke depression (PSD), as well as the location of the stroke. Important factors in diagnosing PSD are the awareness of its potential presence and the ability to distinguish depression from the physical effects of stroke and post-stroke emotionalism.

Emotional disturbances following stroke have long been recognised. Whilst important states such as emotional lability and indifference are common and well recognised, they have received much less interest from the research community than anxiety and especially depressive syndromes occurring after stroke.

Most research looking at the emotional sequelae to stroke has investigated the relationship of stroke to depression and, as studies have generally found an increase in all forms of depression after stroke, the quasi-diagnostic term post-stroke depression (PSD) has been coined.

This term might be understood to imply that depression after stroke has certain unique qualities which mark it out as a distinct syndrome but this is not in fact the case and it appears to be no different from depressive syndromes occurring in other illnesses. However, the term PSD will be used here as it is well recognised and a convenient label.

How Frequent is Depression after Stroke?

Prevalence rates for stroke after depression vary enormously (from 5% to 50%) (Pohjasvaara et al., 1998) depending on several factors, including the criteria used to diagnose depression, stroke severity and how long after the stroke the assessment is made.

Higher rates are reported when broad criteria are applied that encompass all forms of depression whilst rates of about 8% are found when major (severe) depression criteria are applied. Such rates are similar to those reported in association with other severe and disabling illnesses.

Aetiology of Post-stroke Depression

Both psychosocial and physical factors appear to be important in the development of depression after stroke. Disablement has been shown to be a strong predictor of depression (Prince et al., 1997) and consequently the various forms of disability which follow stroke are likely to be an important factor in the development of depression.

As well as the physical impairments, which hinder mobility and communication, there are the consequent social losses, e.g. forced to retire from employment, unable to participate fully as a mother, and the associated impact on self-esteem to consider.

However, the location of the stroke also appears to be important. Early reports suggested frontal stroke and left sided stroke were more strongly associated with depression but other studies disagreed, and a systematic review (Carson et al., 2000) concluded there was no evidence for an association of left hemisphere stroke with depression or for an association of depression with left anterior lesions or with frontal lesions in general.

However, a large MRI study from Finland has reported a significant increase in both the number and the volume of infarcts affecting the frontal-subcortical circuitry, especially on the left side in subjects after stroke (Vataja et al., 2001).

This study is important, not only because of the greater accuracy of MR over CT but because frontalsubcortical circuits are recognised as the neuroanatomical substrate of much of the depression syndrome (Mayberg et al., 2001). It may also be that stroke is a surrogate marker for other vascular disease which is associated with depression rather than itself a cause of depression.

Depression has strong bidirectional relationships with both coronary artery disease (CAD) and stroke (Thomas et al., 2004). There have been many reports in "pure" depression syndromes, especially in older people, of an increase in subcortical lesions in both the white matter and the basal ganglia (O'Brien et al., 1996).

These lesions manifest as hyperintense lesions on MRI and are strongly associated with vascular risk factors and there is pathological evidence that such lesion are indeed due to cerebral ischaemia and cerebrovascular disease (CVD) (Thomas et al., 2002).

Such lesions are common in stroke sufferers and therefore the focus of many studies on cortical stroke disease may have distracted from the importance of subcortical CVD in the aetiology of depression after stroke. The emergence of depression after stroke may be due to the impact of CVD on subcortical brain areas rather than the impact of the stroke on the cortex and adjacent white matter.

Of course, both cortical and subcortical CVD could be important in the aetiology of stroke, but the potential importance of subcortical CVD needs to be considered by clinicians and in future research studies in this field.

Recognising and Diagnosing Post-stroke Depression

Perhaps the most important factor in diagnosing depression after stroke is an awareness of its potential presence. A bewildering array of depressive symptoms occur following stroke, with sleep disturbance, tearfulness, worries being common and guilt, psychotic symptoms and suicidal thoughts being unusual (and the latter should trigger a referral to a psychiatrist).

Lethargy, appetite and sleep disturbance are all important features of depression but not usually helpful in distinguishing depression from the physical effects of stroke. The most helpful features are persistent sadness and anhedonia.

Persistence of any depressive symptoms (not readily explained by physical illness) is important as major depression criteria require features to be present for at least two weeks and transient symptoms are common.

A depressed mood state typically persists day after day but also shows diurnal variation, being more severe in the morning. Depression needs to be distinguished from emotional lability (sometimes referred to as post-stroke emotionalism or catastrophic reactions), emotional indifference, anxiety states and grief at the losses inflicted by the stroke.

Post-stroke emotionalism, reported in about 10% of stroke sufferers (House et al., 1989), is an abnormal lability of mood during which the patient laughs or cries for no easily discernible reason. Typically the patient does not feel the expected emotion associated with this outward reaction.

Careful history taking usually reveals these reactions to be provoked by some kind of stimulus which can be understood to be emotionally moving, e.g. being reminded of a happy event or seeing a picture of a loved one. It is the extent of the reaction that is extreme, and this seems to be due to the loss of the normal control of the emotional response.

These features should enable emotionalism to be distinguished from depression and treatment with low dose (50mg) of a tricyclic antidepressant (Robinson et al., 1993) or an SSRI (Andersen et al., 1993) are often very effective within a few days.

Emotional indifference, as the term implies, is somewhat the opposite, referring to a blunted emotional state more typical of apathy in subcortical disease states. It overlaps with depression and can be difficult to distinguish (Starkstein et al., 1993) but emotional indifference itself is not associated with the inner sadness and anhedonia that occurs in depression, and questions about the patient's inner feelings and desires should enable this state to be elucidated from depression.

Anxiety states, dominated by the physical and mental features of anxiety (trembling, sweating, persistent worries), have been reported in 28% of post-stroke patients (Astrom 1996). Such high levels of symptoms remain constant up to 3 years but they have substantial comorbidity with depression and are likely to improve with the treatment of depression. In the absence of comorbid depression the prognosis for such anxiety is less auspicious.

Prognosis of Post-stroke Depression

It is important to recognise and diagnose depression after stroke. This is not only because of the increased suffering depression causes to patients who already have much to cope with, but because depression after stroke is associated with a worse prognosis and there is evidence that treatment substantially improves this outlook (see treatment below).

Large prospective studies have reported poorer functional outcome at 15 months in patients with depression 3 months after stroke (Pohjasvaara et al., 2001) and a strong correlation of functional outcome and depressive symptoms at both 3 months and 1 year after stroke (Herrmann et al., 1998).

Mortality is also increased in those who develop depression after stroke. Morris and colleagues (Morris et al., 1993) found depression after stroke led to a 3.4-fold increase in mortality up to 10 years after the incident stroke.

Although this bleak finding applied to hospitalised stroke sufferers it has also been shown to be true for a broader range of patients managed in community settings (Everson et al., 1998). These findings are, perhaps, not surprising given that people with depression are sad, withdrawn, poorly motivated and pessimistic and thus prone to poor adherence to pharmacological treatments and rehabilitation.

Treatment of Post-stroke Depression

Although neither physiotherapy (Green et al., 2002) nor psychotherapy (Lincoln and Flannaghan, 2003) appear to improve depression after stroke several studies have reported that treatment with tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs) do lead to substantial improvements in depression. (Lipsey et al., 1984, Robinson et al., 2000).

Whether this is associated with improvements in functioning is less clear with some studies positive (Reding et al., 1986) and others not (Robinson et al., 2000).

However, the importance of pharmacological treatment for PSD has been demonstrated by the finding that after 9 years those treated for depression for 3 months after their stroke had longer survival times (Jorge et al., 2003).

Which antidepressant should a clinician use? Most studies have used TCAs, giving these drugs the largest evidence base, and a direct comparison of the TCA nortriptyline with the SSRI fluoxitene found nortriptyline to produce greater reductions in depression (Robinson et al., 2000).

However, TCAs are known to have significant negative effects on cardiovascular disease and to be associated with higher risk of completed suicide (Glassmann 1998), whilst SSRIs are safe in depression in cardiac diseases (Glassmann et al., 2002) and are associated with improved cardiovascular outcomes (Sauer et al., 2001).

The greater safety of SSRIs in cardiac disease is probably because of their inhibitory effects on platelet activation. The SSRIs are also very likely to be safer in stroke disease than TCAs and this improved safety profile probably makes them the treatment of choice for most people with PSD.

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